Cartridge holder assembly for a drug delivery device

ABSTRACT

The present invention relates to a cartridge holder assembly for a drug delivery device comprising of a cartridge holder adapted to receive a cartridge filled with a medicament to be dispensed by the drug delivery device, wherein the cartridge holder comprises a first through opening at a distal end section to receive a piercing element adapted to penetrate a sealing member of the cartridge, a support structure adjacently arranged to the first through opening; and a constriction member arranged between the support structure and a distal end face of the cartridge and having a second through opening smaller than the first through opening.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. §371 of International Application No. PCT/EP2011/073379 filedDec. 20, 2011, which claims priority to European Patent Application No.10196224.9 filed Dec. 21, 2010. The entire disclosure contents of theseapplications are herewith incorporated by reference into the presentapplication.

FIELD OF THE DISCLOSURE

The present invention relates to drug delivery devices and in particularto pen-type injectors, that is to injectors of the kind that provide toadminister by injection of medicinal products from a multidosecartridge. In particular, the present invention relates to suchinjectors, where a user may set and dispense the dose.

BACKGROUND

User operated drug delivery devices are as such known in the prior art.They are typically applicable in circumstances, in which persons withoutformal medical training, i.e., patients, need to administer an accurateand predefined dose of a medicinal product, such as heparin or insulin.In particular, such devices have application, where a medicinal productis administered on a regular or irregular basis over a short term orlong-term period.

In order to accommodate with these demands, drug delivery devices haveto fulfil a number of requirements. First of all, the device must berobust in construction, yet easy to use in terms of handling and inunderstanding by the user of its operation and the delivery of therequired dose or medicament. Further, the dose setting must be easy andunambiguous. Where the device is to be disposable rather than reusable,the device should be inexpensive to manufacture and easy to dispose.Moreover, the device should be suitable for recycling. To meet theserequirements, the number of parts required to assemble the device andthe number of material types the device is made from need to be kept toa minimum.

The medicinal product to be dispensed by means of the drug deliverydevice is typically provided in a disposable or replaceable cartridge,such as a vial, ampoule or carpule comprising a piston slidably disposedin the barrel of the cartridge. The piston is to be operably engagedwith a piston rod or drive ram of the drug delivery device's drivemechanism. By applying thrust to the cartridge's piston in distaldirection—that is towards the patient in the present context—apredefined dose of the liquid drug can be dispensed and expelled fromthe cartridge.

Cartridges as they are typically used with drug delivery devices, suchas pen-type injectors are typically sealed by means of a septum. Such aseptum is commonly designed as rubber stopper providing an air-tightseal but being pierceable by piercing elements such as needles orcannulae.

A well-known cartridge holder assembly 10 is illustrated in crosssection in FIG. 1. This cartridge holder assembly 10 for a drug deliverydevice comprises a cartridge holder 14 adapted to receive a cartridge12, which is hermetically sealed with a flexible and deformable septum22. At its lower and distal end section, the cartridge holder 14 isthreadedly engaged with a needle mount 16. Said mount or needle holder16 comprises a threaded cylindrical portion allowing to screw the needleholder 16 on the threaded neck portion of the cartridge holder 14. Atits lower and distal end section, the mount 16 comprises a flange-likebottom face 17, which in a concentrically inner section holds theinjection needle or cannula 20.

During an assembly procedure of the needle holder 16, its proximallylocated needle 20 penetrates the septum 22 with a tipped end. In thisway, a fluid-transferring connection for the purpose of dose dispensingcan be established. Additionally, the distal and free end of the needle20 can be provided with a replaceable needle cap 19. Also, the entirecartridge holder assembly 10 can be covered and protected by aprotective cap 18.

Depending on manufacturing tolerances and the mutually correspondingdesign of cartridge 12 and cartridge holder 14, an axial gap 24 ofvariable size is typically formed between the bottom portion 17 of theneedle holder 16 and the distal end face of the cartridge 16. Axial sizeof this free space area 24 may vary, e.g. due to manufacturing andassembly tolerances. In particular, during dispensing of a dose of themedicinal fluid contained in the cartridge 12, a respective fluidpressure is built-up, which, due to the inherent elasticity of theseptum 22, leads to a respective axial expansion of the septum 22. As aconsequence, the septum 22 may almost entirely fill said free space area24 during a dispending procedure.

Due to its elastic properties the septum 22 will store elastic energyduring dose dispensing. But as soon as the fluid pressure returns to aninitial value after a dose dispensing procedure, the septum 22 relaxesinto its initial configuration, which is accompanied by a retraction ofthe expanded section of the septum 22 back into the cartridge 12.However, also such a retracting motion may in turn lead to a built-up ofa non-negligible fluid pressure enhancement and, as a consequence, acertain amount of medicinal fluid may be supplementally expelled fromthe cartridge 12, which can be typically observed in the form ofpost-dispending droplet formation at the distal tip of the needle 20.

It is therefore an object of the present invention, to provide animproved cartridge holder assembly for a drug delivery device, whichcounteracts generation of droplets after termination of a dosedispensing procedure. It is a further object, to provide an effectivemeans adapted to prevent septum deformation during dose dispensing.Furthermore, the invention focuses on an inexpensive as well as on astable and robust design of a drug delivery device.

SUMMARY

The present invention provides a cartridge holder assembly for a drugdelivery device which is adapted to dispense a dose of a medicament ormedicinal product provided in a cartridge. The cartridge holder assemblycomprises a cartridge holder, which is adapted to receive a cartridge,typically designed as vial, carpule or ampoule. Said cartridge isreadily filled or is to be filled with a liquid medicament to bedispensed by the drug delivery device in a well-defined way, typicallyby way of injection.

The cartridge, to be positioned in the cartridge holder is hermeticallysealed in distal direction by means of a flexible and deformable sealingmember, such like a septum, which is penetrable by a piercing element,e.g. by an injection needle or a cannula. The piercing element is to bereleasably mounted on the cartridge holder by way of a needle assemblyto become threadedly engaged with is distal portion with the cartridgeholder. For this purpose, the cartridge holder comprises a first throughopening at its distal end section to receive the piercing element. Thepiercing element is adapted to penetrate the sealing member of thecartridge in order to establish a fluid-transferring coupling to theinside volume of the cartridge.

Additionally, the cartridge holder assembly, in particular the cartridgeholder itself comprises a support structure which is adjacently arrangedto the first through opening. The cartridge holder assembly furthercomprises a constriction member arranged between the support structureof the cartridge holder and a distal end face of the cartridge. Saidconstriction member comprises as second through opening which is smallerin diameter than the first through opening of the cartridge holder. Thisway, the constriction member effectively reduces the diameter of adistally located through opening of the cartridge holder assembly.

The size of the second through opening is designed such that thepiercing element may still penetrate the sealing member disposed insidethe cartridge holder. However, by reducing the diameter of the secondthrough opening, elastic deformation of the cartridge's sealing membercan be effectively counteracted. The constriction member serves as astabilizing structure and reduces elastic deformation of the septum.Hence, the volume and size of a septum extension area between a needleholder and a cartridge holder assembly can be advantageously reduced.

Unintentional expansion of the septum during dose dispending conditionscan be at least reduced or can be entirely inhibited. Due to thestructural stabilization of the sealing member or septum of thecartridge, magnitude and impact of an elastic relaxation process of theseptum after termination of a dose dispensing procedure can beadvantageously reduced, thus providing a respective reduction of dropletgeneration.

According to a preferred embodiment, the constriction member is ofcircular or disc-like shape. Preferably, the overall geometry of theconstriction member is adapted to the geometry and dimensions of thecartridge holder and its support structure. Typically, the cartridgeholder is of substantially cylindrical shape and comprises a respectivecircular symmetric support structure adapted to receive acorrespondingly shaped disc-like constriction member of circular shape.

In another preferred embodiment, the constriction member is designed asan insert piece to be arranged or positioned between the distal end faceof the cartridge and a proximal support face of the support structure.

When the constriction member is designed as a separate piece the size ofthe second through opening provided in the constriction member as wellas the overall geometry of said constriction member may be modified andadapted to a variety of different piercing assemblies or piercingelements. Hence, the diameter of the second through opening arranged inthe constriction member may correspond to the diameter of the piercingelement to be arranged therethrough. Depending on the type of cartridgeto be used, an appropriately dimensioned constriction member with athrough opening of variable diameter can be inserted into the cartridgeholder.

In a further preferred embodiment, first and second through openings areconcentrically arranged with respect to each other. Moreover, firstand/or second through openings may feature similar and/or identicalgeometry. First and second through openings are preferably of circulargeometry.

In still another embodiment, the constriction member comprises a sheetmetal disc. Hence, the constriction member is made of sheet metal andtherefore provides a comparatively rigid and structurally stiffenedstructure, which is able to withstand a distally directed pressureeffect arising or emanating from the elastically deformable septumduring dose dispensing. A sheet metal disc is also very simple andnon-expensive to manufacture and may even allow to equip or to retrofitexisting cartridge holders with a constriction member.

In a further preferred embodiment the sheet metal disc comprises athickness of less than 1 mm, less than 0.5 mm, less than 0.2 mm, or evenless than 0.1 mm or 0.05 mm. Depending on the material of choice for thesheet metal disc, even a very thin disc featuring a thickness in thesub-millimeter range may already provide sufficient structural supportfor effectively counteracting septum deformation during dose dispensing.

By making use of e.g. an aluminum or steel disc, a thickness in therange of sub-millimeters for the sheet metal disc can be attained whichallows to leave the general design and geometry of the cartridge holderalmost unaffected. Hence, by making use of a rather thin stabilizingdisc as the support structure, existing cartridge holders may simply beretrofitted with said constriction member and do not require any furthermodification.

In another aspect, the support structure comprises a radially inwardlydirected flange portion integrally formed with the cartridge holder. Theradially inwardly directed flange portion may even form a distal endface of the cartridge holder. Said flange portion may abut in distaldirection with a bottom face of a needle assembly and said flangeportion may further abut with the constriction member in proximaldirection. Therefore, the radially inwardly directed flange portion mayprovide a distal abutment for the disc-shaped constriction member to besqueezed between the support structure and the cartridge to be mountedin the cartridge holder.

It is of further benefit, when the flange portion circumferentiallysurrounds the first through opening. Having a circumferential flangeportion at the distal end of the cartridge holder, axially, inparticular distally directed mechanical forces can be homogeneouslyabsorbed. Alternatively, the flange portion may comprise numerousradially extending slits, allowing for an at least slight axialdeformation of the flange portion if it becomes subject to respectiveaxially directed mechanical pressure.

In a further preferred embodiment, the radially inwardly protrudingsupport structure comprises at least one proximal abutment surface toreceive the constriction member. Here, it is even conceivable, thatabutment face and constriction member comprise mutually correspondinginterlock means, e.g. in form of mutually corresponding form-fittingelements. This way, unintentional disassembly of constriction member andsupport structure can be effectively prevented in case that thecartridge is removed from the cartridge holder.

In a further advantageous aspect, the constriction member is elasticallydeformable in axial direction when squeezed between the supportstructure and the distal end face of the cartridge. For enhancingelastic deformation of the constriction member, it may comprise one orseveral, e.g. radially extending slits in order to facilitate, tocontrol and/or to modify its generic elasticity. By squeezing theconstriction member, axial pressure between cartridge holder andcartridge may built-up and may be maintained when the cartridge isassembled inside the cartridge holder in its final assemblyconfiguration. Since the constriction member may become subject to anelastic or even plastic deformation during assembly of cartridge holderand cartridge, axial tolerances of the cartridge holder and the entiredrug delivery device can be at least reduced or even entirelyeliminated.

Furthermore, and according to another preferred embodiment, the radiallyinwardly extending abutment face of the support structure is inclined indistal direction, hence towards the free end of the cartridge holder.This way, the inclination of the abutment face of the support structuremay define a respectively inclined elastic deformation of theconstriction member when a final assembly configuration of cartridgeholder, constriction member and cartridge has been reached. Theinclination of the inwardly extending flange of the support structuremay define a maximum degree of elastic deformation of the sheet metaldisc.

This way and according to a further preferred embodiment, theconstriction member is prestressed or elastically deformed and/orcomprises a shape that corresponds with the geometry of the supportstructure, at least when in final assembly configuration.

According to another independent aspect, the invention also provides adrug delivery device for dispensing of a dose of a medicament. Said drugdelivery device comprises a cartridge filled with or to be filled withthe medicinal product to be dispensed. The drug delivery device furthercomprises a drive mechanism, which is operably engaged with thecartridge for dispensing of a predefined dose of the medicament.Further, the drug delivery device is characterized by a cartridge holderassembly as described above.

In another but further independent aspect, the invention also provides amethod of assembly of a drug delivery device that comprises a cartridge,a drive mechanism and a cartridge holder assembly as described above.The method is characterized by an assembly procedure for assemblingcartridge holder and cartridge of a drug delivery device, in particulara pen-type injector. Here, a constriction member is positioned at adistally located support structure of a cartridge holder prior to anassembly of cartridge holder and cartridge. The constriction memberserves to reduce the free diameter of a first and distal through openingof the cartridge holder in order to provide a structural stabilizationmeans for the sealing member of the cartridge and to counteract distallydirected expansion of the cartridge's sealing septum during dosedispensing.

The term “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a protein, apolysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, anantibody, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(w-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

-   H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   wherein the group -Lys6-NH2 may be bound to the C-terminus of the    Exendin-4 derivative;    or an Exendin-4 derivative of the sequence-   H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,-   H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]    Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(S1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2;-   or a pharmaceutically acceptable salt or solvate of any one of the    afore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

It will be further apparent to those skilled in the pertinent art thatvarious modifications and variations can be made to the presentinvention without departing from the spirit and scope of the invention.Further, it is to be noted, that any reference signs used in theappended claims are not to be construed as limiting the scope of thepresent invention.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following, preferred embodiments of the invention will bedescribed in greater detail by making reference to the drawings inwhich:

FIG. 1 schematically illustrates a cartridge holder assembly incross-sectional view according to the prior art,

FIG. 2 illustrates a cross-sectional sketch of a cartridge holderassembly according to first embodiment, and

FIG. 3 illustrates a comparable cross-sectional view of the cartridgeholder assembly according to a second embodiment.

DETAILED DESCRIPTION

FIGS. 2 and 3 schematically illustrate a distal end section of acartridge 12 positioned inside a respective distal end portion of acartridge holder 14. The cartridge holder 14 is illustrated in FIGS. 2and 3 with a stepped-down neck portion adapted to receive a respectivedistal neck portion of a cartridge 12. The illustrated distal end of thecartridge 12 comprises a sealing element, e.g. a penetrable orpierceable septum 22 which is kept in position on top of the body of thecartridge 12 by way of an aluminum cap 34 embracing the distally locatedhead section of the cartridge 12 and the septum 22. The cartridge holder14, preferably manufactured as an injection moulded thermoplasticcomponent comprises a radially inwardly protruding and circumferentialflange portion 40 at its distal end. As illustrated in FIG. 2, saidflange portion 40 serves as a support structure for a disc-shapedconstriction member 36 preferably comprising a sheet metal disc.

The illustrated distal end section of the cartridge holder 14 comprisesan outer thread 26 that corresponds with an inner thread 28 of a needleassembly 16, which is to be screwed onto the cartridge holder 14 untilthe needle assembly 16 abuts with a distally located flange portion 40of the cartridge holder with its bottom section 17.

The constriction member 36 serves as a bearing or abutment for thedistal end face of the cartridge 12. As can be seen in FIGS. 2 and 3,the metal disc 36, 46 comprises a concentric through opening 44 which issmaller than the free diameter between oppositely located flangeportions 40, 42. The through opening 30 of the cartridge holder 14 canbe reduced in diameter by means of the constriction members 36, 38.

In this way, an elastic and distally directed deformation or bulgedportion 32 of the septum 22 during a dose dispensing action can be atleast reduced in size. Consequently, a respective post-dispensingrelaxation effect can be reduced and a resulting droplet generation tobe observed at a distal but illustrated tip of the needle 20 can beeffectively reduced or even anihilated.

As further illustrated in the alternative embodiment according to FIG.3, the radially inwardly protruding support structure 42 comprises aninclined support or abutment surface 46 facing in proximal direction. Byway of such an inclined abutment surface 46, axial and elasticdeformation of the constriction member 38 can be limited. In any of theillustrated embodiments according to FIGS. 2 and 3, the constrictionmember 36, 38 may become subject to mechanical and axially directedpressure or stress and may therefore provide or establish permanentmechanical stress or tension between the cartridge 12 and the cartridgeholder 14, thus effectively eliminating inevitable axial tolerances.

The constriction member 36, 38 may be provided as a separate insertpiece and may therefore allow to retrofit also existing cartridge holderassemblies featuring a radially inwardly protruding flange portion 40,42. Since the metal disc may feature a thickness in the sub-millimeterrange, preferably between 0.1 mm and 0.2 mm or even below 0.1 mm, theoverall design and geometry of an existing cartridge holder 14 mayremain almost unaffected.

Moreover, depending on the type of needle 20 to be penetrated orinserted through the septum 22 of the cartridge 12, transverse size ofthe diameter of the constriction member's 36, 38 central through opening44 may vary.

1-10. (canceled)
 11. Cartridge holder assembly for a drug deliverydevice comprising: a cartridge holder adapted to receive a cartridgefilled with a medicament to be dispensed by the drug delivery device,wherein the cartridge holder comprises a first through opening at adistal end section to receive a piercing element adapted to penetrate asealing member of the cartridge, a support structure adjacently arrangedto the first through opening; characterized by a a constriction memberof circular or disc-like shape arranged between the support structureand a distal end face of the cartridge and having a second throughopening smaller than the first through opening, wherein the supportstructure comprises a radially inwardly directed flange portionintegrally formed with the cartridge holder which comprises a proximalabutment surface to receive the constriction member.
 12. The cartridgeholder assembly according to claim 11, wherein the second throughopening is concentrically arranged with the first through opening. 13.The cartridge holder assembly according to claim 11, wherein theconstriction member comprises a sheet metal disc.
 14. The cartridgeholder assembly according to claim 13, wherein the sheet metal disccomprises a thickness of less than 0.2 mm, less than 0.15 mm, less than0.1 mm or even less than 0.05 mm.
 15. The cartridge holder assemblyaccording to claim 14, wherein the flange portion circumferentiallysurrounds the first through opening.
 16. The cartridge holder assemblyaccording to claim 11, wherein the constriction member is elasticallydeformable in axial direction when squeezed between the supportstructure and the distal end face of the cartridge.
 17. The cartridgeholder assembly according to claim 15, wherein the radially inwardlyextending abutment face is inclined in distal direction.
 18. Thecartridge holder assembly according to claim 17, wherein theconstriction member is prestressed and/or comprises a shape thatcorresponds with the geometry of the support structure.
 19. A drugdelivery device for dispensing of a dose of a medicinal product,comprising: a cartridge filled with the medicinal product, a drivemechanism operably engaged with the cartridge to dispense a predefineddose of the medicinal product, a cartridge holder assembly according toclaim
 10. 20. A method of assembly of a drug delivery device comprisinga cartridge, a drive mechanism and a cartridge holder assembly accordingto claim 10, wherein a constriction member is positioned at a distallylocated support structure of a cartridge holder prior to an assembly ofcartridge holder and cartridge.